ClinVar Miner

Submissions for variant NM_001128840.3(CACNA1D):c.3701A>G (p.Asn1234Ser)

dbSNP: rs147146258
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000609862 SCV000711557 uncertain significance not specified 2016-08-24 criteria provided, single submitter clinical testing The p.Asn1254Ser variant in CACNA1D has not been previously reported in individu als with hearing loss, but has been identified in several populations by the Exo me Aggregation Consortium including 0.1% (39/66732) of European chromosomes (ExA C, http://exac.broadinstitute.org; dbSNP rs147146258). Although this variant has been seen in the general population, its frequency is not high enough to rule o ut a pathogenic role. Computational prediction tools and conservation analyses d o not provide strong support for or against an impact to the protein. In summary , the clinical significance of the p.Asn1254Ser variant is uncertain.
GeneDx RCV001584414 SCV001811942 likely benign not provided 2022-06-01 criteria provided, single submitter clinical testing See Variant Classification Assertion Criteria.
Labcorp Genetics (formerly Invitae), Labcorp RCV001584414 SCV002278517 likely benign not provided 2025-01-19 criteria provided, single submitter clinical testing
CeGaT Center for Human Genetics Tuebingen RCV001584414 SCV002563774 uncertain significance not provided 2023-07-01 criteria provided, single submitter clinical testing
Ambry Genetics RCV004024888 SCV004915194 uncertain significance Inborn genetic diseases 2022-09-19 criteria provided, single submitter clinical testing The c.3761A>G (p.N1254S) alteration is located in exon 30 (coding exon 30) of the CACNA1D gene. This alteration results from a A to G substitution at nucleotide position 3761, causing the asparagine (N) at amino acid position 1254 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Centre de Biologie Pathologie Génétique, Centre Hospitalier Universitaire de Lille RCV001251924 SCV001427670 likely benign Intellectual disability 2019-01-01 no assertion criteria provided clinical testing
Genetic Services Laboratory, University of Chicago RCV000609862 SCV003839302 uncertain significance not specified 2022-12-05 no assertion criteria provided clinical testing DNA sequence analysis of the CACNA1D gene demonstrated a sequence change, c.3761A>G, in exon 30 that results in an amino acid change, p.Asn1254Ser. This sequence change does not appear to have been previously described in individuals with CACNA1D-related disorders. This sequence change has been described in the gnomAD database with a frequency of 0.05% in the overall population (dbSNP rs147146258). The p.Asn1254Ser change affects a highly conserved amino acid residue located in a domain of the CACNA1D protein that is known to be functional. In-silico pathogenicity prediction tools (SIFT, PolyPhen2, Align GVGD, REVEL) provide contradictory results for the p.Asn1254Ser substitution. Due to insufficient evidences and the lack of functional studies, the clinical significance of the p.Asn1254Ser change remains unknown at this time.

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