ClinVar Miner

Submissions for variant NM_001845.6(COL4A1):c.196C>A (p.Gln66Lys)

gnomAD frequency: 0.00002  dbSNP: rs751220553
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CeGaT Center for Human Genetics Tuebingen RCV000995091 SCV001149091 uncertain significance not provided 2022-07-01 criteria provided, single submitter clinical testing
Invitae RCV000995091 SCV002311959 uncertain significance not provided 2024-01-13 criteria provided, single submitter clinical testing This sequence change replaces glutamine, which is neutral and polar, with lysine, which is basic and polar, at codon 66 of the COL4A1 protein (p.Gln66Lys). This variant is present in population databases (rs751220553, gnomAD 0.01%). This missense change has been observed in individual(s) with congenital anomalies of the kidney and urinary tract (PMID: 31230195). ClinVar contains an entry for this variant (Variation ID: 807047). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on COL4A1 protein function. 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.
Fulgent Genetics, Fulgent Genetics RCV002497298 SCV002790210 uncertain significance Autosomal dominant familial hematuria-retinal arteriolar tortuosity-contractures syndrome; Brain small vessel disease 1 with or without ocular anomalies; Hemorrhage, intracerebral, susceptibility to; Retinal arterial tortuosity; Microangiopathy and leukoencephalopathy, pontine, autosomal dominant 2021-12-01 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV003424522 SCV004117414 uncertain significance COL4A1-related condition 2023-05-20 criteria provided, single submitter clinical testing The COL4A1 c.196C>A variant is predicted to result in the amino acid substitution p.Gln66Lys. This variant was reported in individuals with Congenital anomalies of the kidney and urinary tract (Table 1, Kitzler et al. 2019. PubMed ID: 31230195). This variant is reported in 0.012% of alleles in individuals of Latino descent in gnomAD (http://gnomad.broadinstitute.org/variant/13-110866311-G-T). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
Yale Center for Mendelian Genomics, Yale University RCV001849465 SCV002106633 likely pathogenic Congenital anomaly of kidney and urinary tract 2019-06-22 no assertion criteria provided literature only

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