ClinVar Miner

Submissions for variant NM_001082538.3(TCTN1):c.956T>G (p.Leu319Arg)

gnomAD frequency: 0.00001  dbSNP: rs762127242
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Laboratory Services, Illumina RCV001111503 SCV001269065 uncertain significance Joubert syndrome 13 2018-01-12 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Labcorp Genetics (formerly Invitae), Labcorp RCV001856481 SCV002287734 uncertain significance Familial aplasia of the vermis; Meckel-Gruber syndrome 2022-02-27 criteria provided, single submitter clinical testing In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 882102). This variant has not been reported in the literature in individuals affected with TCTN1-related conditions. This variant is present in population databases (rs762127242, gnomAD 0.003%). This sequence change replaces leucine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 319 of the TCTN1 protein (p.Leu319Arg).
Ambry Genetics RCV004032164 SCV004962021 uncertain significance Inborn genetic diseases 2024-01-23 criteria provided, single submitter clinical testing The c.956T>G (p.L319R) alteration is located in exon 8 (coding exon 8) of the TCTN1 gene. This alteration results from a T to G substitution at nucleotide position 956, causing the leucine (L) at amino acid position 319 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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